Allylic and Propargylic Alcohols

Boireau, D. Abenhaim, J. Bourdais, and E. Henry-Basch, Tetrahedron Letters, 1976, 4781. 

Allyl amine oxides, chiral at either nitrogen (23) or an adjacent carbon (25), show complete transfer of asymmetry to the alcohol carbon in their [2,3]sigma- 

The Pd-catalysed arylation of tertiary allylic alcohols with aryl halides (equation 4), in the presence of a base, produces aryl substituted allyl alcohols in varying yields, and a mechanistic scheme has been proposed. 

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Double bonds in conjugation to a carbonyl group and allylic and propargylic alcohols. But the isolated double and triple bonds are inert. 

The isomerisation of allyl and propargylic alcohols involves the 1,3-shift of an oxygen atom rather than a hydrogen atom. Isomerisation of allyl alcohols can be catalysed by a variety of metal oxo complexes and in this instance the reaction does not involve metal carbon bonds as we will see. One could imagine that allylic metal species can participate in isomerisation of allylic compounds, but for the alcohols themselves this is not an easy reaction. In chapter 13 reactions of allyl acetates and the like, which are more prone to... 

Scheme 18 Coupling of an allenylidene ligand with allyl and propargyl alcohol...

Shortly after this work, Shibasaki and coworkers developed a useful method for the substitution of allyl and propargyl alcohols using Bi(OTf)3 [61]. Various amines such as tosylamine, carbamates, amides and cinnamylamide yielded allyl and propargyl amides 27a-h and 25g-h in excellent yields (Scheme 21). The addition of KPF6 was... 

Scheme I Working hypothesis to activate allylic and propargylic alcohols using a Bi catalyst via cj-71 chelation...

Methyl perfluoromethacrylate reacts with allyl and propargyl alcohols to give the Michael addition products 19 and 20, respectively these eliminate hydrogen fluoride in the presence of the boron trifluoride-triethylamine complex and rearrange to acyl fluorides 21 and 22. Hydrolysis of the acyl fluorides with base results in decarboxylation to give the 2-(trifluoromethyl) esters 23 and 24.11... 

The bromocyclization of A/,jV-dialkylaminomethyl ethers of allyl and propargyl alcohols to form oxa-zolidinium salts has been reported, but not used in synthesis.255 The heterocyclization of /V-acylamino-methyl ethers with mercury salts has been used for stereoselective synthesis of a variety of 1,2-amino alcohol systems. These cyclizations form rans-4,5-dialkyl oxazolidine products with good to excellent stereoselectivities (equation 120 and Table 33). As shown by entry 5, 6-endo cyclization predominates (6 3) with an internal double bond of ( )-configuration, but this mode of cyclization is reduced with substrates containing a (Z) double bond and/or allylic oxygen substitution (Table 33, entries 6-9). 

Benzylic, allylic, and propargylic alcohols can be oxidized by o-iodosylbenzoic acid (IBX) 7 in the presence of stabilized Wittig ylides to generate a>/3-unsaturated esters 30 in a one-pot procedure, Scheme 11. This is useful when the intermediate aldehydes are unstable and difficult to isolate [70]. 

With regard to diorganozincs other than primary dialkylzincs, various diorganozincs such as divinylzinc (> 96% ee, addition to benzaldehyde),4 difurylzinc (72% ee, addition to benzaldehyde),5 diphenylzinc (78-82% ee, addition to various aldehydes),6 and diisopropylzinc (93% ee, addition to benzaldehyde)7 have been utilized in the chiral (3-aminoalcohol catalysed reactions. Alkenyl(alkyl)zincs4b,c and alkynyl(alkyl)zincs8 afford the corresponding chiral allylic and propargyl alcohols. 

Activation of allylic and propargylic alcohols. These alcohols can couple with Grignard reagents in the presence of an a-chloroenamine. For this purpose the related reagent l-chloro-2-methyl-N,N-tetramethylenepropenyIamine (2) is more effective than 1. 

The formation of alkanenitriles from alcohols and HCN is of no interest for laboratory preparations. However, a large number of publications, particularly patents, have appeared, which deal with technical applications of this procedure. A few review articles " serve very well as introductions to this field. Under particularly mild conditions allyl and propargyl alcohols can be transformed into the corresponding nitriles with hydrogen halides in the presence of Cu salts. - The possibility of generating nitriles from alcohols via the analogous halides needs no further treatment at this stage. 

Wittig reaction. Allylic and propargylic alcohols undergo the Wittig reaction with stabilized ylides in the presence of MnOj, after in situ oxidation. 

Suginome and Ito have developed a reliable method for the synthesis of highly enantioenriched allyl- and allenylsilanes. The synthetic process involves 1,3-chirality transfer from homochiral allyl and propargyl alcohols through Pd-catalyzed intramolecular bis-silylation and subsequent Peterson-type elimination (Scheme 10.142) [395]. This method provides an efficient route to enantioenriched allylsilanes bearing a hydroxyalkyl group, which are very valuable as synthetic intermediates for diastereo- and enantioselective synthesis of heterocycies and carbocycles [396]. Polymer-supported highly enantioenriched allylsilanes have been prepared from enantioenriched allyl alcohols and a polymer-supported disilanyl chloride [397]. 

TsCl, TEA, MesNHCl, toluene, 80-97% yield. With this method allylic and propargylic alcohols can be tosylated without chloride formation. ... 

A-Alkylation of sulfonamides occurs at room temperature with benzylic, allylic and propargylic alcohols in the presence of Bi(OTf)3 and KPFg." ... 

E)-AUylsilanes and allenylsilanes. The preparations from allylic and propargylic alcohols via the (silyl)silyl ethers involve bis(organosilyl)Pd(II) complexes to insert into the multiple C-C bonds and a subsequent yyn-elimination of the ensuing oxasilacyclobutanes to afford the products and PhjSi=0. 

The chiral rhenium complexes of allylic and propargylic alcohols 841 are selectively oxidized by IBX to the unsaturated carbonyl compounds 842 in good yields (Scheme 3.334) [1139]. 

A one-pot oxidation of benzylic, allylic and propargylic alcohols, as well as diols, with IBX in the presence of the stabilized Wittig ylide 843 affords a,p-unsaturated esters 844 in generally good yields (Scheme 3.335) [1140]. This is a useful one-pot procedure because the intermediate aldehydes are often unstable and difficult to isolate. 

The efficiency of this oxidation was also evaluated by comparison to other oxidations, such as the Dess-Martin, pyridinium dichromate and Swern oxidations. It was demonstrated that the hypervalent iodine(V)-catalyzed oxidation could be applied for almost all types of fluorinated alcohols and it was comparable to Dess-Martin oxidation, while pyridinium dichromate and Swern oxidations could not be employed for allylic and propargylic alcohols as well as the alcohols having an aliphatic side chain. Additionally, the hypervalent iodine-catalyzed oxidation could be applied for a larger scale reaction (Scheme 4.49) without any decrease in reaction efficiency [81]. 

The addition of a-sulfinyl carbanions to carbonyl compounds followed by further functional group modification has proved to be an efficient and highly stereoselective approach to epoxides, a-aminoketones, a-aminoaldehydes, a-hydroxy esters, and allylic and propargylic alcohols [76-80]. 

As summarized in Table 3.1, catalysts 1-11 have provided good-to-excellent results for the KR of a wide range of unsaturated (functionalized) alcohols, such as benzylic, allylic and propargylic alcohols. 

Srikrihsna [12] also used the microwave heating technique and observed, with triethyl orthoacetate and propionic acid as catalyst in dimethyl formamide, a dramatic rate enhancement in the rearrangement of various allylic and propargylic alcohols (Scheme 6.4). 

The protection of hydroxyl groups as methoxymethyl (MOM) ethers was achieved in a simple and convenient solvent-free reaction on alumina under sonication (Eq. 54).The reactions are generally reasonably fast and high-yielding and conditions are mild enough not to induce isomerization of double or triple bonds in allylic and propargylic alcohols. Alumina can be recycled after washing and reactivation. Without sonication, reactions were very slow. 

The reaction is applicable to benzylic, allylic, and propargylic alcohols. The chlorides listed in Table 4.1 were each made from the corresponding alcohol in less than 15 min at room temperature, with the exception of propargyl chloride. Although the chloroformate of propargyl alcohol formed in less than 1 min, gentle warming was necessary to drive the reaction to completion. 

The direct nucleophilic substitution reactions (Scheme 2) [16-22], restricted mainly to n-activated alcohols such as secondary arylmethanols, allylic and propargylic alcohols, and tertiary alcohols that can readily form stable carbocationic intermediates, are mechanistically different to hydrogen autotransfer reactions. Although these reactions are not the focus of this chapter, since they are also very relevant research areas, this brief introduction is anticipated to provide potentially helpful references to assist interested researchers in their studies, especially in boardline research where elucidation of reaction mechanisms is difficult. 

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